Molecular Mechanisms Through Which Ticks Evade Host Defense

Abstract

Ticks seriously affect mammals and immunization of host is considered as sustainable option for their management. Identification and validation of protective molecules are major challenges in developing vaccines against ticks. Based on understanding tick saliva-host interaction, efforts have been dedicated to tick control to diminish their deleterious effects. By utilization of tick saliva proteins previously identified by cDNA phage display library, transcriptomic and immune-proteomic studies, current study focuses on investigation of roles of 15 selected Amblyomma americanum and Ixodes scapularis recombinant tick saliva proteins (rTSPs) on host macrophage function. The effect of rTSPs on macrophage secretion of pro- and anti-inflammatory cytokines (TNF-, IL-1, IL-6, IL-10, TGF-β) was investigated. Moreover, the functional role was examined by in vivo paw edema assay, cytokine and chemokine analysis. In vitro and in vivo investigations show that five Amblyomma americanum rTSPs, AamIGFBP (Insulin like growth factor binding proteins) rP-1, AamIGFBP-rP6 Short (S) and AamIGFBP-rP6 Long (L), Serine protease inhibitor (serpin) 8 (AAS8) and AamTCI (tick carboxypeptidase inhibitor), out of 15 are pro-inflammatory (PI) rTSPs as revealed by expression of pro-inflammatory costimulatory markers, cytokines, chemokines and signaling molecules. Interestingly, the two rTSPs serpins, AAS27 and AAS41, are anti-inflammatory (AI) rTSPs and appear to reverse the expression of costimulatory markers and cytokines induced by LPS and PI-rTSPs. Results indicate that PI- and AI-rTSPs function in host evasion and thus may serve as potential candidate for anti-tick vaccination.